Abstract of Research Plan. During the past three decades a wide variety of cross reactions between microbial and mammalian tissues have been noted. An example par excellence has been the group A. streptococcus both from the point of view of the diversity of its reactions as well as the number of diseases associated with these interactions. These cross reactions coupled with evidence for a genetic predisposition in one of these diseases makes these interactions a fertile field of study concerning Microbial-Host-Immunogenetics interactions. It is, therefore, the purpose of this proposal to study these interactions from the following points of view. We will further isolate and characterize a newly described genetic marker for rheumatic fever individuals and study its relationship to the immune response to streptococal antigens in the normal and diseased individuals. A corollary of these studies will be to explore the question of whether this genetic marker is present on other tissues and whether it might serve as a receptor or recognition site for streptococcal antigens. A second major area will be the pursuit of the isolation and characterization of those tissue antigens which share antigenic determinants with streptococcal antigens. The major emphasis will be on those organs which are involved in post-streptococcal sequelae. A corollary of these studies will be to determine at what level embryonic, differentiation, histocompatibility) these cross reactions between Microbes and Host occur. It is hoped that further knowledge gained from the streptococcal Microbial-Host system may have broad implications for Microbial-Host interactions in other disease states.